Orphan Drug Outlook and the Management of These Agents

The U.S. Food and Drug Administration (FDA) currently has about 200 pending orphan drug designation requests, according to experts at a session on the orphan drugs in the development pipeline and strategies for managing these expensive therapies.

Last year, the FDA released a “90 in 90 Plan,” which states that in 90 days the FDA will complete reviews of all orphan drug designation requests that are older than 120 days. After 90 days, 100% of all new requests will receive a response by the agency within 90 days of receipt.

Furthermore, in December 2017 the FDA issued draft guidance that it will no longer grant orphan drug designations to pediatric subpopulations unless the disease constitutes a valid orphan subset and the sponsor can adequately demonstrate that the disease in the pediatric population is different from that of adults, as well as meeting all other criteria for this designation.

During a presentation at AMCP Annual Meeting 2018, Christine Bui, PharmD, BCPS, a drug information pharmacist, and Stephen Jung, PharmD, BCPS, a manager of drug information, both of MedImpact Healthcare Systems, Inc., highlighted drugs in development for key rare disease areas and current management strategies.

Disease states in which products are under development include:

  • Spinal Muscular Atrophy (SMA), a rare, autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord, resulting in severe and progressive atrophy of skeletal muscles and generalized weakness. In 2016, nusinersen was approved for SMA in adults in children. The phase III SMA pipeline includes AVXS-101 and RG7916.
  • Ceroid Lipofuscinosis Type 2 (CLT2), an autosomal recessive, neurodegenerative lysosomal storage disorder caused by deficiency of tripeptidyl peptidase 1 enzyme. In 2017, cerliponase alfa was approved to slow the loss of ambulation in symptomatic pediatric patients with late infantile CLN2. The phase I/II CLN2 pipeline includes AAVrh10, which is a gene therapy.
  • Amyotrophic Lateral Sclerosis (ALS), a rapidly progressing neurodegenerative disorder characterized by motor neuron degeneration in the spinal cord, brainstem, and motor cortex. In 2017, edaravone was approved for ALS. The phase III ALS pipeline includes masitinib and NurOwn, which is a stem cell therapy.

Payer sensitivity of these agents continues to rise, as annual costs range in the hundreds of thousands per patient and few—if any—have alternative agents available for the rare disease. As a result, payers have changed the benefit design to manage utilization and spend, which includes formulary restrictions and specialty tier, shifting from copayments to coinsurance, and using prior authorization.

An analysis of reimbursement data found that orphan drugs have more coverage restrictions than non-orphan drugs, with prior authorizations used most widely. Prior authorization criteria for these agents include documentation of clinical diagnosis, appropriate patient age, prescriber specialty, baseline data (including genetic screening and laboratory values), renewal criteria (including documentation of response), and quantity limit.

Presentation S4: The Rise of Orphan Drugs: The Increasingly Common Challenge of Managing Rare Diseases. AMCP Annual Meeting 2018.